The production of interferon (IFN) after stimulation of peripheral blood mononuclear cells with Sendai virus or phytohemagglutinin was studied in patients with common variable immunodeficiency (CVID) or selective IgA deficiency. Cells from CVID patients produced significantly more Sendai virus-induced (alpha) and mitogen-induced (gamma) IFN than cells from healthy control subjects. By contrast, some patients with selective IgA deficiency produced subnormal amounts of IFN-alpha. Neither IFN-alpha nor IFN-gamma was detectable in sera from the two categories of patients using radioimmunoassays with sensitivity limits of 5-10 international units per milliliter. With the aid of a more sensitive bioimmunoassay, however, antiviral activity was detected more frequently in sera from patients with CVID than in sera from control individuals. Acid treatment and absorption with anti-IFN-alpha and anti-IFN-beta sera indicated that the antiviral activity was due to IFN, with no preponderance of any particular IFN type. Determination of beta-2-microglobulin (beta 2M) concentrations revealed that CVID patients had markedly, and IgA-deficient patients moderately increased serum levels of this substance, as compared to healthy blood donors. Since IFN enhances the synthesis of beta 2M the finding of increased levels of this substance in CVID would be consistent with the observed hyperproduction of IFN. The present findings are concordant with earlier observations of increased natural killer cell activity in at least some forms of CVID and suggest that increased activity of the IFN/natural killer cell system provides a mechanism which may compensate for the defective B cell function in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)